Development and Persistence of Tissue-Level Musculoskeletal Deformity Following Brachial Plexus Birth Injury

点击翻译按钮获取中文摘要

Project Summary Brachial Plexus Birth Injury (BPBI) is a neuromuscular injury that causes lifelong arm impairments and deformities in the glenohumeral joint which restricts mobility of the upper limb. Little is known about the progression of bone and muscle growth in the postnatal period following BPBI. The parent grant explores key drivers of deformity progression including the timeline of development and resultant functional effects through a rat model consisting of different injury locations and unloading (preganglionic and postganglionic neurectomy, disarticulation, and sham groups). The primary hypothesis is that the key driver in BPBI bone deformity is the mechanical environment due to impaired longitudinal growth of paralyzed muscle and altered active functional loading beginning shortly after injury. The proposed work will further the parent research by investigating active loading of the glenohumeral joint during functional gait in a rat model. Bone readily adapts to its mechanical environment, so analysis of its organized microstructures would also provide insight to key mechanical drivers of microstructural deficits. Supplement Aim 1. Determine how limb loading is altered during functional gait following BPBI. Rationale: Spatiotemporal characteristics of gait are substantially and differentially altered during walking in rats following pre- and postganglionic neurectomy. However, the forces experienced on each limb at the ground and on the developing glenohumeral joint are unknown and are likely important drivers of glenohumeral development. Supplement Aim 2. Determine how active limb loading during functional gait drives morphological and microstructural changes in the glenoid. Rationale: Our unique co-simulation computational model of glenohumeral growth and function has been used to directly relate specific deformity and contracture features to isolated changes in passive muscle force, active range of motion, and biological growth rate; however, actual limb usage and its mechanical relationship to bone material properties and trabecular organization has not yet been explored. Altered gait and limb loading during walking and running after neurectomy will be evaluated to explore how limb usage and loading is affected by BPBI. Spatiotemporal motion data and ground contact forces will be recorded for each animal and compared among groups. Resultant gait data will be integrated into the computational simulation of glenohumeral loading and adaptation during active limb function following BPBI. Tissue properties will be validated using micro-computed tomography (micro-CT) images of the internal bone density and microstructure of the scapula and humerus collected under the R01 project and used to identify the portion of bone response due to active loading. A micro-CT-based micro-scale finite element model will provide tissue stress and yielding patterns to elucidate loading-driven adaptations in trabecular organization. The proposed supplement work will advance the originally planned modeling approach by including dynamic limb loads and new methods to actively predict bone material property changes and trabecular organization adaptations over the time of limb development.